Continuing support is requested for years 35-40 of the Yale Predoctoral Training Program in Human Genetics and Genomics. The program involves 49 trainers from 15 departments. The vast majority of trainers are primary and joint appointees in the Department of Genetics at the School of Medicine, and virtually all of the trainees over the last funding period have been matriculated in the Molecular Cell Biology, Genetics & Development Track (MCGD) in Biological and Biomedical Sciences at Yale. The focus of the training proposed is the use of genetic and genomic approaches to understand human disease. The main methods used are newly developed next generation sequencing methods for human trait locus discovery, complemented by bioinformatics and computational analysis. An emphasis of the program is integration with model system genetics and genomics, which can be used to define pathways that link gene mutations to disease phenotypes. To this end, investigators performing genetic and genomic analysis of flies, worms, zebrafish, mouse and induced pluripotent stem cells play a major role in this Training Grant. This integrated training environment is intended to provide trainees with broad exposure to genetics and genomics and a rich training environment that prepares them for careers in science. Admitted students have strong scientific backgrounds and research experience with high academic achievement. First year students are supported by Yale; students are supported by the training grant in years 2 and 3, and thereafter by funds in Training Faculty laboratories until graduation. Training in the first year includes formal course work and research rotations, leading to selection of the thesis advisor and laboratory. In the second year, students complete course work, and take a qualifying exam in which they must demonstrate mastery of genetics and defend two written research proposals. Subsequent years are devoted to dissertation research, development of experimental and analytic skills, along with ability in written and oral presentation, leading to preparation of the written thesis. In addition, students engage in supervised teaching experiences. Support is requested for 5 years for support of 7 Ph.D. students per year who are in years 2 and 3 of their training. Outcomes of trainees are documented and indicate high success in completion of the Ph.D., publication of work in high impact journals, and continuation in science of the vast majority of graduating students.